Human cytomegalovirus is the prototypical member of the beta-herpesvirus family. Seroepidemiologic studies have shown that human cytomegalovirus infection is widespread in the human population. In healthy individuals infection is generally asymptomatic, but the virus can cause serious disease in people with immature or compromised immune systems. It is the leading infectious disease cause of birth defects and a life-threatening adventitious agent in transplant recipients and AIDS patients. The long-term objective of this research program is to elucidate the function of human cytomegalovirus genes that regulate the interaction of the virus with its host cell and thereby control the processes of viral replication and pathogenesis. This proposal will study human cytomegalovirus proteins that are delivered to the cell as constituents of the virion. These proteins have the potential to exert profound effects on the virus-host interaction, because they are present at the very start of the infectious process. My specific aims follow: (1) Investigate the function and biochemical activities of the UL83-coded pp65 protein; (2) Investigate the function and biochemical activities of the UL69 protein. (3) Investigate the function and biochemical activities of the UL32-coded pp150 protein. (4) Investigate the function and biochemical activities of the UL48 protein. Our studies will include analysis of both a laboratory strain (AD169) and a clinical isolate (VR1814, FIX) of the virus.